Schisandrin A suppresses lipopolysaccharide-induced inflammation and oxidative stress in RAW 264.7 macrophages by suppressing the NF-κB, MAPKs and PI3K/Akt pathways and activating Nrf2/HO-1 signaling

Kwon,Da  Hye; Cha,Hee-Jae; Choi,Eun  Ok; Leem,Sun-Hee; Kim,Gi-Young; Moon,Sung-Kwon; Chang,Young-Chae; Yun,Seok-Joong; Hwang,Hye  Jin; Kim,Byung  Woo; Kim,Wun-Jae; Choi,Yung  Hyun

doi:10.3892/ijmm.2017.3209

Schisandrin A suppresses lipopolysaccharide-induced inflammation and oxidative stress in RAW 264.7 macrophages by suppressing the NF-κB, MAPKs and PI3K/Akt pathways and activating Nrf2/HO-1 signaling

Authors:
- Da Hye Kwon
- Hee-Jae Cha
- Eun Ok Choi
- Sun-Hee Leem
- Gi-Young Kim
- Sung-Kwon Moon
- Young-Chae Chang
- Seok-Joong Yun
- Hye Jin Hwang
- Byung Woo Kim
- Wun-Jae Kim
- Yung Hyun Choi
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Affiliations: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 47227, Republic of Korea, Department of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267, Republic of Korea, Department of Biological Science, College of Natural Sciences, Dong-A University, Busan 49315, Republic of Korea, Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea, Department of Food and Nutrition, College of Biotechnology and Natural Resource, Chung-Ang University, Anseong 17546, Republic of Korea, Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 42472, Republic of Korea, Personalized Tumor Engineering Research Center, Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea, Department of Food and Nutrition, College of Nursing, Healthcare Sciences and Human Ecology, Dongeui University, Busan 47340, Republic of Korea, Department of Life Science and Biotechnology, College of Engineering, Dongeui University, Busan 47340, Republic of Korea
Published online on: October 25, 2017 https://doi.org/10.3892/ijmm.2017.3209
Pages: 264-274
Copyright: © Kwon et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Schisandrin A is a bioactive lignan occurring in the fruits of plants of the Schisandra genus that have traditionally been used in Korea for treating various inflammatory diseases. Although the anti-inflammatory and antioxidant effects of lignan analogues similar to schisandrin A have been reported, the underlying molecular mechanisms have remained elusive. In the present study, schisandrin A significantly suppressed the lipopolysaccharide (LPS)-induced production of the key pro-inflammatory mediators nitric oxide (NO) and prostaglandin E2 by suppressing the expression of inducible NO synthase and cyclooxygenase-2 at the mRNA and protein levels in RAW 264.7 macrophages. Furthermore, schisandrin A was demonstrated to reduce the LPS-induced secretion of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β; this was accompanied by a simultaneous decrease in the respective mRNA and protein levels in the macrophages. In addition, the LPS- induced translocation of nuclear factor-κB (NF-κB), as well as activation of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol‑3 kinase (PI3K)/Akt pathways were inhibited by schisandrin A. Furthermore, schisandrin A significantly diminished the LPS-stimulated accumulation of intracellular reactive oxygen species, and effectively enhanced the expression of NF erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). These results suggested that schisandrin A has a protective effect against LPS-induced inflammatory and oxidative responses in RAW 264.7 cells by inhibiting the NF-κB, MAPK and PI3K/Akt pathways; these effects are mediated, at least in part, by the activation of the Nrf2/HO-1 pathway. Based on these results, it is concluded that schisandrin A may have therapeutic potential for treating inflammatory and oxidative disorders caused by over-activation of macrophages.

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